Achieving Sufficient Accrual to Address the Primary Endpoint in Phase III Clinical Trials from US Cooperative Oncology Groups.

Publication Type:

Journal Article

Source:

Clinical cancer research : an official journal of the American Association for Cancer Research, Volume 18, Issue 1, p.256-262 (2012)

Keywords:

2012, Achievement, Adolescent, Benchmarking, Center-Authored Paper, Child, Clinical Trials, Phase III as Topic, Humans, Neoplasms, November 2011, Patient Selection, Prognosis, Public Health Sciences Division, Research Design, United States

Abstract:

PURPOSE: Assessing impact of poor accrual on premature trial closure requires a relevant metric. We propose defining accrual sufficiency on apparent ability to address primary endpoints (PE) rather than attaining accrual targets. EXPERIMENTAL DESIGN: All phase III trials open 1/1/1993-12/31/2002 by five US oncology clinical trial cooperative groups (CTCG) were evaluated for accrual sufficiency and scientific results. Sufficient accrual included meeting accrual target, CTCG documentation attesting adequate accrual, or conclusive results at interim analysis; insufficient accrual included poor accrual as cited closure reason or other reasons rendering a trial unable to address its PE. Closure rates based on our accrual sufficiency definition are compared to rates of meeting accrual targets and addressing the PE. A percent of target accrual above which trials commonly answer the intended scientific question was identified to serve as an alternative to meeting full target accrual in designating accrual success.RESULTS: Of 238 eligible trials, 158 (66%) closed with sufficient accrual. Among 80 trials with insufficient accrual, 70 (29%) closed specifically due to poor accrual. Inadequate accrual rates are overemphasized when defining accrual success solely by meeting accrual targets. Nearly 75% of trials conclusively addressed the PE with positive results in 39% of trials. Exceeding 80% of target accrual serves as a reliable proxy for answering the intended scientific question. CONCLUSIONS: Approximately one-third of phase III trials closed with insufficient accrual to address the PE, primarily due to poor accrual. Defining accrual sufficiency broader than meeting accrual targets represents a fairer account of trial closures.